Clinical and experimental immunology最新文献

Introduction: Despite the high global prevalence of Mycobacterium tuberculosis (Mtb) infection in humans, most infected individuals achieve a stable immunological equilibrium, without showing clinical signs and symptoms of tuberculosis (TB). Although the role of antibodies in TB is assumed to be relatively small compared to cell-mediated immunity, their role in TB has been documented in a few recent studies.

Methods: In this cross-sectional study, we quantitated antibody responses to Mtb antigens, lipoarabinomannan (LAM), and heparin-binding hemagglutinin adhesin (HBHA) by determining antigen-specific immunoglobulin A(IgA) and G(IgG) secretion levels using enzyme-linked immunosorbent assay (ELISA) in serum and saliva of pulmonary TB patients (PTB), their household contacts (HHC), and community controls (CC) (determined by QuantiFERON TB Gold assay QFT- test result).

Results: The HBHA-specific IgA levels were significantly higher in both saliva and serum in HHC groups compared to PTB patients (P=0.013, P=0.023). Exposed contacts, who were QFT-negative had higher serum HBHA-specific IgA responses compared to PTB patients (P=0.04). QFT-negative HHC and QFT-positive CC showed higher HBHA and LAM-specific IgG responses (P=0.006, P=0.002, P=0.0009, P=0.006, respectively) than PTB patients. Generally, LAM and HBHA-specific IgA levels were significantly higher in saliva compared to serum (P<0.0001) in all study groups.

Conclusion: Overall, the observed higher levels of IgA and IgG in controls, and exposed but QFT-negative contacts suggest a correlation with, and perhaps a role for these antibodies in preventing the development of active TB. The findings highlighted the potential involvement of saliva IgA in the immune response to Mtb, underscoring the relevance of mucosal immunity in TB infection.

T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. Twenty-one responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17-shifted phenotype. The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.

Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterized. Here we focussed on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular overabundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.

Introduction: T regulatory (Treg) cells play a crucial role in immune system homeostasis and in the pathogenesis of immune-mediated inflammatory diseases. Accordingly, numerous studies have examined the number and function of these lymphocytes in patients with different conditions as well as in healthy controls. The aim of this study was to analyze potential variations in the number and function of two Treg cell subsets in healthy adults over a 2-month period.

Methods: In a pilot study, blood samples were collected from 20 healthy individuals on Days 0, 30, and 60, and the levels of natural Treg cells (CD4+CD25highFoxp3+) and CD69+ Treg cells (CD4+CD69+CD25-/+LAP+IL-10+Foxp3-) were analyzed by flow cytometry. In addition, the function of these regulatory cells was evaluated using an in vitro assay that measures the inhibition of activation of autologous T lymphocytes.

Results: Although no significant differences were observed across the three serial measurements of the number or function of the Treg cells analyzed (P > 0.05 in both cases), a substantial proportion of individuals showed notable changes (either an increase or decrease) in these parameters during the study. These variations were not apparently associated with any factors affecting immune system homeostasis, including infections, medication use, or immunizations.

Conclusion: Our findings suggest that significant fluctuations of causes to be determined occur in the levels and function of Treg cells in healthy individuals. This phenomenon should be considered in studies investigating immunoregulation in humans.

Introduction: Although celiac disease (CD) current and only treatment is a life-long strict gluten-free diet (GFD), some patients suffer from persistent duodenal lesions despite years into the diet. Hence, we aimed to study the effect that the GFD elicits on the mucosal immune infiltrate from these patients.

Method: To that end, duodenal biopsies were collected from non-celiac controls and CD patients, both at diagnosis and after at least one year into the GFD. The profile of duodenal intraepithelial lymphocytes (lymphogram) and the lamina propria immune infiltrate were determined by spectral cytometry.

Results: At diagnosis, all CD patients had mucosal atrophy, a compatible lymphogram, and an expansion of lamina propria NK cells, innate lymphoid cells, B-cells, Treg and Tγδ cells, all of them expressing high levels of Fas, and Integrins α4 and β7. However, despite all GFD-treated patients had negative serology, 68.4% of them displayed persistent villous atrophy (Marsh score ≥ 3), while 73.3% had a compatible lymphogram. Nevertheless, despite such persistent atrophy, the lamina propria mucosal immune infiltrate was normalized in all GFD-treated patients. Besides, time on the GFD, but not the persistence of mucosal atrophy, correlated with an increased expression of gut-homing migration markers on lamina propria effector T-cells from these patients.

Conclusion: Hence, we hereby have proved how the lamina propria immune infiltrate, as opposed to intraepithelial lymphocytes, is normalized in GFD-treated CD patients despite persistent villous atrophy, suggesting that the epithelial layer may be the driver of such paradoxical persistent mucosal inflammation.

Cytokine storm can result from uncontrolled pro-inflammatory cytokines released in SARS-CoV-2 infection that cause damage to several organs. Il-6 is one of the major mediators of cytokine storm. IFN-α2 has been reported to have anti-viral potential and the pre-infection levels of pro-inflammatory cytokines have been suggested to drive the fate of the disease. There is a paucity of information on how anti-viral cytokines at the onset of infection affect the disease progression. This study aims to profile IL-2, IL-6, IL-10, and IFN-α2 expression levels for 44 days post-diagnosis and their effects on recovery. Peripheral venous blood was collected from 38 SARS-CoV-2 infected participants who came for diagnosis at the Centre for Research on Emerging and Re-emerging Diseases. IL-2, IL-6, IL-10, and IFN-α2 levels were measured using a Luminex panel. Males had higher SARS-CoV-2 viral load than females, although the difference was not statistically significant (P = 0.08). Age-related variation was also observed, with individuals aged 40-60 showing significantly higher viral load than those over 60 (P = 0.045). Cytokines analysis revealed that males had significantly higher levels of IFNα-2, IL-2, and IL-6 (P = 0.0031, P = 0.009, and P = 0.022 respectively) than females upon diagnosis, with cytokines levels decreasing over time in males but increasing in females. Cytokine levels trended higher in symptomatic individuals, although differences were not significant. These findings highlight the influence of sex, clinical status, and viral load on cytokine dynamics in COVID-19, with potential implications for understanding disease severity and immune response.

Children with recurrent infections present a diagnostic challenge due to the wide overlap between normal childhood infections and primary immunodeficiency diseases. Predominantly antibody deficiencies are the most common category of primary immunodeficiency disease in this population. While many predominantly antibody deficiency cases are identified through markedly low immunoglobulins levels or reduced B cell counts, some demonstrate subtler forms such as IgG subclass deficiency or specific antibody deficiency, which may present similar clinical symptoms but normal standard laboratory parameters. Diagnosing these conditions in children is particularly challenging due to the overlap with physiological immune immaturity and the high incidence of infections in early childhood. Clinicians must carefully distinguish between benign infection patterns and true immunodeficiencies to avoid missed diagnoses and unnecessary investigations. This review summarizes key findings on IgG subclass deficiency and specific antibody deficiency, highlights their clinical relevance in paediatric practice, and evaluates current challenges in diagnosis and classification. We also discuss the overlap between these conditions and propose a structured approach to improve diagnostic consistency. Addressing these knowledge gaps is essential to optimize care for children with recurrent infections and suspected antibody deficiencies.

Reactive oxygen species (ROS) are produced in immune cells by the phagocyte NADPH oxidase (NOX2) system that carries out coordinated transfer of electrons to molecular oxygen. The importance of the system in host defence and immunoregulation is underlined by chronic granulomatous disease (CGD), a severe monogenic immunodeficiency caused by mutations in genes encoding individual components of NOX2. CGD also leads to inflammatory manifestations due to the regulatory role of ROS in multiple signalling processes. We describe the system in detail, from its discovery to our current understanding of the oxidase. We also describe CGD and illustrate how recent insights into this disease shed light on physiology.

Deficiency of adenosine deaminase 2 (DADA2) has been a challenging diagnosis to make since it was first described in 2014. The disease represents a wide range of phenotypes. Therefore, it may present with various clinical patterns. Throughout the years, several difficult-to-diagnose cases of DADA2 were reported in the literature. Although several studies and reviews were published regarding different phenotypes and manifestations of DADA2, a review of challenging cases with diverse combinations of DADA2 manifestations was needed to integrate the knowledge from the literature into the clinical practice. Immunological, hematologic, autoinflammatory, and adult-onset polyarteritis-nodosa patterns were reported in the literature as cases challenging to diagnose. In this review, we aim to summarize the challenging case reports from the literature, provide an algorithmic approach for these kinds of presentations, and share our perspective and recommendations on the topic. Diagnosing DADA2 on time is a vital issue for preventing fatal and debilitating vascular events with anti-TNF-alpha therapy. Thus, early testing for DADA2 in suspected cases is recommended. Family history and genetic testing of the patient and the first-degree relatives are essential for accurate diagnosis. Thorough systemic examination and imaging might help detect clinically silent findings of vasculitis. Enzymatic activity of ADA2, when available, is also a key diagnostic tool that complements genetic testing and clinical evaluation.